1. Field of the Invention
The present invention relates to a diagnostic composition for Alzheimer's disease which includes an agent measuring the methylation level of HMOX1 (Heme oxygenase 1) gene promoter, a diagnostic kit and a method for diagnosing Alzheimer's disease using the same.
2. Description of the Related Art
Alzheimer's disease (AD) is a representative degenerative brain disorder that results in degeneration of nerve cells, leading to loss of cognitive ability and memory. It progresses over time and eventually leads to death due to other complications. Alzheimer's disease can occur in people in their forties or fifties, and the incidence of Alzheimer's disease increases with age approaching 40 to 50% at the age of 85 to 90.
As the number of those with Alzheimer's disease is increasing rapidly with the current aging of the population, the need for early diagnosis, prevention and treatment is growing. However, the diagnosis of Alzheimer's disease has been made only by neuropsychological tests (e.g., mini-mental state examination (MMSE)) or specialized MRI scans which require much time and cost.
Other biochemical methods have been also proposed for the diagnosis of Alzheimer's disease, for example, a method for detecting the level of beta amyloid protein or tau protein in the cerebrospinal fluid or serum, a method for detecting glial fibrillary acidic protein (GFAP)-antibody or the like. However, convenience and accuracy of the diagnostic methods are still in doubt (International Patent Publication No. 92/17152; U.S. Pat. No. 4,666,829; International Patent Publication No. 89/06242; U.S. Pat. No. 5,231,000, etc.).
Meanwhile, HMOX1 (Heme oxygenase 1) is a heat shock protein 32 (HSP32) that exists in the endoplasmic reticulum, and it binds with NADPH cytochrome p450 reductase to convert a pro-oxidant heme to CO, Fe2+ and biliverdin which is subsequently converted to an antioxidant bilirubin by biliverdin reductase. The conversion of biliverdin to bilirubin contributes to protection of cells from oxidative stress. However, there have been no reports that epigenetic changes in the methylation status of HMOX1 gene promoter can be used for the diagnosis of Alzheimer's disease.
The present inventors have found Alzheimer's disease-specific hypomethylation of HMOX1 gene promoter. They have confirmed that diagnosis of Alzheimer's disease can be made by measuring the methylation level of HMOX1 gene promoter using a biomarker, thereby completing the present invention.